CHICAGO (EGMN) –More than half of liver transplant recipients survive 20 years with intact graft function, and enjoy a quality of life better than do most patients with chronic conditions, according to a prospective long-term outcome analysis.

After marking more than 25 years since the University of California Los Angeles (UCLA) had its first liver transplant on Feb. 1, 1984, program founder and chief Dr. Ronald W. Busuttil and his colleagues opted to revisit some of those early recipients. The goal was to learn more about long-term allograft function and the little-studied outcome of quality of life (QOL).

The 293 transplant recipients comprised 179 adults and 114 children treated between 1984 and 1988. The researchers found that 163 (56%) survived for 20 years.

Actuarial 10- and 20-year survival was 56% and 52%, respectively, for patients and 49% and 42% for grafts, Dr. Busuttil said at the annual meeting of the American Surgical Association.

The 20-year survivors were significantly more likely to be pediatric patients and women, reflecting the preponderance of biliary atresia in children and primary biliary cirrhosis in females – two of the top three indications for transplantation, along with hepatitis C. Urgent transplantation, higher total ischemia time, biliary complication, and retransplantation were significantly more likely to have occurred in nonsurvivors.

Biopsy proven acute or chronic graft rejection occurred in 30% of the 293 patients. Twenty-year survivors were significantly more likely than were nonsurvivors to have an episode of rejection (35% vs. 27%) but were less likely to have multiple episodes of acute rejection (5% vs. 12%) or to progress from acute to chronic rejection (19% vs. 29%), Dr. Busuttil said. Also, the interval from transplantation to the first episode of rejection was longer: 18 months in survivors vs. 5 months in nonsurvivors.

Socioeconomic rehabilitation in this population was dramatic, he said. Among 38 pediatric and 39 adult patients available for analysis, 74% of pediatric and 85% of adults completed high school, and 19% and 30% completed college. Half of the pediatric recipients and 72% of adults were employed, retired, or homemakers. More than one-third (37%) of pediatric patients and 87% of adults were married, with intact marriages reported in 79% and 69%.

Completion of the Medical Outcomes Study: 36-Item Short Form-Health Survey by 68 of the 20-year survivors revealed strong mental health, but a lag in physical health. When compared with standard published data for the U.S. general population, survivors reported significantly higher scores in the mental health category; comparable scores in the categories of bodily pain, mental component, emotional well-being and vitality, and lower scores in five categories including physical functioning and general health, he said.

When asked by an audience member what might explain this physical lag, Dr. Busuttil said that survivors pay the price for taking toxic medications for 20 years, in terms of such side effects as kidney failure and a de novo malignancy rate of 15%.

Most important, scores for 20-year survivors were higher in all 10 categories when compared with published data for patients with chronic liver disease, and were higher or comparable to scores for patients with chronic heart failure or type II diabetes mellitus in all categories, Dr. Busuttil said.

The 20-year survivors also reported significantly higher social support scores on the Medical Outcomes Study, compared with published data from 1,000 healthy persons aged 18-88 years. They also had higher memory function and lower global, neurologic impairment on the Neuropsychological Impairment Scale.

“Our results confirm the promise offered by this procedure to patients with an otherwise fatal condition,” Dr. Busuttil said.

Invited discussant Dr. Göran Klintmalm, chair and chief of the Baylor Regional Transplant Institute in Dallas, said it is important to understand how transplant recipients live, not just that they survive. He called the quality-of-life outcomes remarkable and was reassured by the neuropsychological findings because of concerns over toxicity observed in transplant recipients given calcium inhibitors and cyclosporine.

Dr. Klintmalm questioned whether more could be done to optimize pediatric outcomes and whether ischemia time should be an issue in the national debate, having only been recently re-discovered as an important paradigm in transplant efforts. Total ischemia time in the study was significantly shorter in 20-year survivors at 6.2 hours, vs. 8.7 hours in nonsurvivors.

Dr. Busuttil acknowledged that many pediatric patients become noncompliant and said that, in the last year, UCLA has established a transition clinic to help move adolescents from pediatric to adult care. “These are the patients who are most vulnerable,” he said, adding that strategies need to be explored to more accurately identify who can be weaned from immunosuppression or given alternative medications such as mammalian target of rapamycin (mTOR) inhibitors.

Dr. Busuttil said he is opposed to any new organ allocation scheme that would increase cold ischemia time, noting that for every 50-100 miles that a donor organ has to travel, cold ischemia time is increased by about 1-2 hours.

Dr. Busuttil had no disclosures.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

芝加哥(EGMN)——一项前瞻性长期结果分析发现，超过半数的肝移植患者可存活20年，且移植肝功能完好，并且其生活质量(QOL)要好于多数慢性肝病患者。

 

加州大学洛杉矶分校(UCLA)于1984年2月1日进行首例肝移植至今已逾25年，该项目创始人和首席专家Ronald W. Busuttil 博士及其同事回访了这些早期肝移植患者。其目的在于了解更多关于移植肝长期功能和少有人研究的生活质量结果。

 

于1984~1988年接受肝移植的293例患者中，成人为179例，儿童为114例。研究者发现，其中163例(53%)已存活20年。

 

Busuttil博士在美国外科学会年会上报告，患者的10年和20年精确生存率分别为56%和52%，而移植肝分别为49%和42%。

 

存活20年的患者更多为儿童和女性，这体现了儿童胆管闭锁和女性原发性胆汁性肝硬化的发生率较高，这是3种肝移植适应证中的2种，另外一种为丙型肝炎。紧急移植、总缺血时间较长、胆道并发症和再移植者更有可能死亡。

 

活检显示293例患者中的30%发生了急性或慢性移植物排斥反应。Busuttil博士说，与死亡者相比，存活20年者更易发生排斥反应(35%对27%)，但更少发生多次急性排斥反应(5%对12%)，也更少由急性转为慢性排斥反应(19%对29%)。另外，其移植后至发生首次排斥反应的间隔时间也更长：存活者为18个月，死亡者为5个月。

 

Busuttil博士说，这一人群的社会经济重建效果显著。在可用于分析的38例儿童和39例成人患者中，74%的儿童和85%的成人完成了高中学业，且分别有19%和30%上了大学。其中半数儿童和72%的成人患者后来有工作、已退休或是主妇。超过1/3(37%)的儿童和87%的成人患者后来结了婚，并且其中分别有79%和69%的患者婚姻未受影响。

 

医学结果研究：由存活20年患者中的68例完成的36项简表健康调查发现，其心理健康较好，但身体健康状况较差。当与已发表的针对美国大众的标准数据相比，存活者自报的心理健康评分明显较高；肌体疼痛、心理功能、情绪健康和活力方面的评分与标准数据相当；而包括肌体功能和一般健康的其他5类指标的评分较低。

 

当与会者问及如何解释存活者身体健康状况较差的问题时，Busuttil博士说，存活者付出了连续服用20年毒性药物的代价，而其副作用包括肾功能衰竭，并且移植肝再次发生恶变的风险为15%。

 

Busuttil博士说，最重要的是，与已发表的慢性肝病患者的资料相比，存活20年者的所有10类评分均较高，而其所有评分均高于慢性心脏功能衰竭或2型糖尿病患者，或与之相当。

 

在医疗结果研究中，与已发表的来自1,000位年龄为18~88岁的健康者的数据相比，存活20年者还报告其社会支持评分显著较高。神经心理病损量表发现，存活者记忆功能较好，而总体神经损害评分较低。

 

Busuttil博士说：“我们的结果验证了这种治疗方法为患者带来的希望，否则这些患者可能病死。”

 

来自达拉斯Baylor地区移植研究所的特邀评论员Göran Klintmalm博士说，了解移植患者的存活情况而不仅仅是是否存活，非常重要。他表示，该研究获得的患者生活质量的结果引人注目，并且其中神经心理的结果进一步消除了他对接受钙抑制剂和环孢素的移植患者毒性方面的顾虑。

 

Klintmalm博士质疑是否可进一步改善儿童移植者的治疗结果，缺血时间是否应作为一个问题进行全国论证(其近期才再次被发现为移植治疗中的一个重要范式)。该研究中，存活20年者的总缺血时间显著短于死亡者(分别为6.2和8.7h)。

 

Busuttil博士承认，一些儿童移植者的依从性降低，去年UCLA成立了一个过渡诊所来帮助青少年患者从儿科到成人医护过渡。他说：“这些都是最脆弱的患者。”他还表示，需要探索新的方法来确定哪些患者可能停用免疫抑制剂或给予哪些患者替代药物，如哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂。

 

Busuttil博士表示他反对任何可能增加冷缺血时间的新的器官分配方案，他指出，供体器官每移动50~100英里的距离，其冷缺血时间就会增加1~2h。

 

Busuttil博士无冲突声明。

 

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